The main objectives of this proposal are to: 1) establish the structural basis for the glomerular filtration of proteins in the normal glomerulus; 2) establish the structural basis for proteinuria in the abnormal glomerulus; and 3) establish the permeability of peritubular capillaries to proteins and other macromolecules, the distribution of such macromolecules in the intercellular spaces, the structural features of endothelial cells and intercellular spaces which subserve these properties, and to relate these observations to the functional role of peritubular capillaries, intercellular spaces, basement membranes and interepithelial cell junctions in renal physiology. To achieve these objectives, protein and macromolecular ultrastructural tracers of various molecular sizes will be used to elucidate the permeability properties of the structural entities involved, the distribution of the tracers, the pathways whereby they pass across structural barriers, and the structural features of the barriers to passage. In addition, by special fixation methods, an isoporous substructure of the slit diaphragm which may be a filtration barrier, has been established and is being studied under normal and abnormal conditions.